In the thymus, the autoimmune regulator (AIRE) induces the transcription of a broad array of organ-specific genes, resulting in the production of proteins that are normally restricted to peripheral tissues. This ectopic expression creates an "immunological self-shadow" that exposes developing T cells to peripheral antigens, thereby facilitating the negative selection of self-reactive T cells and promoting
central tolerance. This discovery was achieved through the combined efforts of researchers in
Diane Mathis' lab— including
Mark Anderson (immunologist)—and those in the
Christopher Goodnow lab, where
Adrian Liston led this work. Studies have shown that AIRE is also expressed in a subset of stromal cells in secondary lymphoid tissues, though these cells express a distinct set of tissue‐restricted antigens compared to medullary thymic epithelial cells. It is important that self-reactive
T cells that bind strongly to self-
antigen are eliminated in the thymus (via the process of
negative selection), otherwise they may later encounter and bind to their corresponding self-antigens and initiate an autoimmune reaction. So the expression of non-local proteins by AIRE in the thymus reduces the threat of
autoimmunity by promoting the elimination of auto-reactive
T cells that bind antigens not normally found in the thymus. Furthermore, it has been found that AIRE is expressed in a population of
stromal cells located in
secondary lymphoid tissues, however these cells appear to express a distinct set of TRAs compared to mTECs. Research in
knockout mice has demonstrated that AIRE functions through initiating the
transcription of a
complete spectrum of self-antigens in the
thymus. The
AIRE gene is also expressed in the 33D1+ subset of
dendritic cells in mouse and in human dendritic cells. == Structure ==